Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2020 Mar;87(4):745-752.
doi: 10.1038/s41390-019-0614-2. Epub 2019 Oct 22.

A clinical score to guide in decision making for monogenic type I IFNopathies

Hafize Emine Sönmez  1 , Cagatay Karaaslan  2 , Adriana A de Jesus  3 , Ezgi Deniz Batu  1 , Banu Anlar  4 , Betül Sözeri  5 , Yelda Bilginer  1 , Dilara Karaguzel  2 , Deniz Cagdas Ayvaz  6 , Ilhan Tezcan  6 , Raphaela Goldbach-Mansky  3 , Seza Ozen  7
Affiliations
Comparative Study

A clinical score to guide in decision making for monogenic type I IFNopathies

Hafize Emine Sönmez et al. Pediatr Res. 2020 Mar.

Abstract

Objective: To develop a set of clinical criteria that identifies patients with a potential autoinflammatory IFNopathy.

Methods: Based on a literature review, a set of clinical criteria identifying genetically confirmed monogenic IFNopathies was selected. For validation, the clinical score was assessed in healthy controls (HCs) and 18 disease controls, including 2 known autoimmune IFNopathies, juvenile systemic lupus erythematosus (JSLE, n = 4) and dermatomyositis (JDM, n = 4); adenosine deaminase 2 deficiency (DADA2, n = 4); and oligoarticular juvenile idiopathic arthritis (oJIA, n = 6). We assessed an IFN score (IRG-S) in whole blood by NanoString using a previously published 28-gene-IRG-S and a reduced 6-gene-IRG-S.

Results: The 12 patients with a possible IFNopathy had higher clinical scores (3-5) than the patients with sJLE, JDM, DADA2, and oJIA and in HCs. Both the 28-IRG-S and 6-IRG-S were significantly higher in the autoinflammatory IFNopathy patients compared to HCs and oJIA and DADA2 patients but not different from patients with JSLE and JDM. Subsequently, genetic analysis revealed mutations in genes previously reported in genes related to the IFN pathway in 9 of the 12 patients.

Conclusion: We developed a clinical score to identify patients with possible autoinflammatory IFNopathies. A clinical score was associated with a high IRG-S and may serve to identify patients with an autoinflammatory IFNopathy.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Interferon (IFN) scores of patients and controls
See this image and copyright information in PMC

References

    1. McDermott MF et al.Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97, 133–144 (1999). - PubMed
    1. Crow YJ & Type I IFNopathies: a novel set of inborn errors of immunity. Ann. NY Acad. Sci 1238, 91–98 (2011). - PubMed
    1. de Jesus AA, Canna SW, Liu Y & Goldbach-Mansky R Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu. Rev. Immunol 33, 823–874 (2015). - PMC - PubMed
    1. Kretschmer S, Lee-Kirsch MA & Type I IFN-mediated autoinflammation and autoimmunity. Curr. Opin. Immunol 49, 96–102 (2017). - PubMed
    1. Kim H, Sanchez GA & Goldbach-Mansky R Insights from Mendelian IFNopathies: comparison of CANDLE, SAVI with AGS, monogenic lupus. J. Mol. Med. (Berl.) 94, 1111–1127 (2016). - PMC - PubMed

MeSH terms

Substances